Crohn's disease is a chronic intestinal inflammatory disease of unknown etiology. One theory of pathogenesis is that it results from an abnormality of immunoregulation resulting in an unrestrained response to a ubiquitous intestinal antigen. We are testing this theory by analyzing T cell suppressor pathways in normal individuals and patients with Crohn's disease. Previous work from this laboratory has shown that the T cell population in lamina propria of the intestine differs from that in the peripheral blood in that the former population contains a much larger fraction of cells bearing a phenotype associated with helper-inducer function (Leu3+8-) and a much smaller fraction of cells having the phenotype associated with suppressor-inducer function (Leu-3+8+) and suppressor-effector function (Leu-2+15+). In the present studies we examined antigen-non-specific immunoregulatory capacity of T cell populations derived from peripheral blood and lamina propria. The results indicate that peripheral blood Leu-3+ cells contain a Leu-3+8+ subpopulation with suppressor function. This is shown by the fact that when increasing numbers of Leu-3+ cells (which contain the Leu 3+8+ subpopulation) is cultured with normal B cells one obtains decreasing Ig synthesis. In addition, mixtures of Leu 3+8+ cells suppress indicator cultures containing Leu-3+8- cells and B cells. A different picture is obtained for lamina propria T cells wherein one finds no decrease in Ig synthesis occurring with increasing numbers of Leu3+ T cells. These findings are surprising in that they suggest that the Leu-3+8+ cells act, at least in part, on other Leu-3+ cells. In addition, they explain the fact that the lamina propria, in containing fewer Leu 3+8+ T cells than peripheral blood manifests less suppressor function. These results will be applied to the analysis of immunoregulatory cell function in Crohn's disease, in which case specific abnormalities of suppressor-inducer function will be sought.